Sudden Cardiac Death in the Young: A Strategy for Prevention by Targeted Evaluation

Abstract

The annual incidence of sudden cardiac death (SCD) in the general population is estimated as 1 in a 1,000. Since survival rates from out-of-hospital cardiac arrests are poor, primary prevention is key to reducing the burden of SCD in the community. Prominent causes of SCD include ischaemic heart disease, anomalous coronary arteries, and the primary myocardial diseases: hypertrophic cardiomyopathy, dilated cardiomyopathy, and ar rhythmogenic right ventricular cardiomyopathy (ARVC). In 4% of sudden deaths in the 16–64 age group, post-mortem examination fails to identify a cause, yielding a default diagnosis of sudden arrhythmic death syndrome (SADS). The inherited arrhythmia syndromes (long QT, short QT, and Brugada syndromes, and familial catecholaminergic polymorphic ventricular tachycardia) may be implicated in SADS, owing to their propensity for producing ventricular tachyarrhythmia in the structurally normal heart. Monogenic disorders therefore predominate as causes of SCD in the young. The advent of effective therapies for these diseases, particularly implantable cardioverter defibrillators, has prompted calls for universal screening to enable timely diagnosis of occult cardiac disease. Since prospective cardiac assessment of the general population is not feasible, the solution may be to target high-risk subgroups, namely, patients with cardiac symptoms, relatives of SCD victims, and competitive athletes. The recommended preliminary work-up includes a 12-lead ECG, signal-averaged ECG, transthoracic echocardiogram, exercise test, and ambulatory ECG monitoring. Cardiovascular magnetic resonance is a useful adjunct in patients with suspected ARVC or anomalous coronary arteries. Provocative challenge with a sodium challenge blocker may be of value in unmasking the Brugada syndrome. Identification of disease-causing mutations in affected individuals facilitates cascade screening of families.

Induced Brugada-Type Electrocardiogram, a Sign for Imminent Malignant Arrhythmias

“…1,2 Because patients with Brugada syndrome usually become symptomatic at a relatively young age, early diagnosis is crucial to prevent SCD in those with a higher risk of developing an arrhythmic event. 3 Approximately one fourth of the cases of Brugada syndrome are caused by loss of function mutations in the cardiac sodium channel SCN5A. Several nongenetic factors have been mentioned in the literature as possible inductors of the ECG pattern resembling Brugada syndrome.…”

The Implications of Inheritance for Clinical Management

“…The experienced clinician may, however, be able to discern a pattern from the findings in the extended family; for example, right precordial T-wave inversion in a parent, combined with arrhythmia of right ventricular origin in 1 or more siblings, raises suspicion of arrhythmogenic right ventricular cardiomyopathy, a disease commonly missed on autopsy. 7,49 Perhaps the most important impact of proven heredity is in lowering the threshold necessary for diagnosis of the trait in relatives. In the index case, a key challenge in establishing the diagnosis is the exclusion of phenocopies: nonhereditary states that mimic the genetically determined disease.…”

“…The most well-known precipitants include swimming and diving for LQT1 (KCNQ1), auditory stimuli for LQT2 (KCNH2), and sleep for LQT3 (SCN5A), underscoring the importance of determining the circumstances of any sudden deaths in the family. 8,49 Regardless of whether the family history suggests a particular subtype, however, a definitive clinical diagnosis of long QT syndrome merits mutation screening of the main causal genes to enable predictive testing and guide treatment. Beta-blocker therapy, for example, is particularly efficacious in LQT1 patients, but perhaps less so in LQT2 and LQT3.…”

Inter Association Task Force Recommendations on Emergency Preparedness andManagement of Sudden Cardiac Arrest in High School andCollege Athletic Programs: A Consensus Statement

“…In about 2% of sudden deaths in young athletes, postmortem examination fails to identify a structural cardiac cause of death. 1,9,10 These deaths may be due to inherited arrhythmia syndromes and ion channel disorders such as long QT or short QT syndrome, Brugada syndrome, or familial catecholaminergic polymorphic ventricular tachycardia (VT). 1 Vigorous exercise appears to be a trigger for lethal arrhythmias in athletes with occult heart disease.…”